SMARCA4 Deficient Thoracic Sarcoma Presenting with a Pathologic Fracture of Proximal Tibia and L5 Vertebral Body: a Case Report and Review of Literature. (28th October 2020)

• Record Type: Journal Article
• Authors: Elzamly, S; Murzabdillaeva, A; Taha, H; Shitawi, M; Zhu, H
• Is Part Of: American journal of clinical pathology. Volume 154(2020)Supplement 1
• Page Start: S40
• Page End: S41
• Publication Date: 2020-10-28
• Subjects: Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqaa161.085
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Introduction/Objective: SMARCA4 (BRG1) is a central component of the Switch/Sucrose-Non-Fermentable (SWI/SNF) chromatin remodeling complex which plays a critical role in the initiation, progression and dedifferentiation of a variety of cancers arising in different anatomical sites. The recently discovered SMARCA4-deficient thoracic sarcoma (DTS) can present as a mediastinal, pleural or pulmonary mass and constitutes a unique and highly lethal entity. Methods: Here we present an interesting case of a 66-year-old, smoker male with past medical history of COPD, polysubstance abuse, hepatitis C virus, and alcoholic cirrhosis who presented with left proximal tibia pathological fracture, L5 vertebral body lytic lesion, left leg cellulitis and hypercalcemia. Imaging studies, tibia biopsy, thoracocentesis, histopathological examination, and immunohistochemical stains were performed. Results: Imaging studies revealed a 3.1 cm, right upper lobe speculated lung mass along with multiple other lung nodules. Numerous arterially enhancing hepatic masses up to 2.8 cm were also identified. The patient underwent intramedullary nail, cementation and tibia biopsy followed by thoracentesis a month later.The histological sections revealed sheets of poorly differentiated malignant epithelioid cells showing high nuclear pleomorphism, prominent nucleoli, eosinophilc cytoplasm with extensive necrosis, and high mitosis (Ki-67 around 100%). The tumor cells lacked the expression of SMARCA4 (BRG1), cytokeratin, SALL4, CD34, TTF-1, P40, S100, HMB45, pan melanoma, desmin, CD31, ERG, CD30, CD56, chromogranin, CD38, CD45, CD3, ALK-1, myeloperoxidase, glypican-3, hepatocyte, and inhibin with mixed kappa and lambda. Tumor cells expressed SATB2 and focal synaptophysin, consistent with SMARCA4 deficient thoracic sarcoma metastasizing to the bone. The patient's condition rapidly deteriorated and he died within two months. Conclusion: An accurate diagnosis of these tumors is paramount and can be challenging. However, recognizing SMARCA4-DTS from other types of epithelioid tumors that involve the thoracic region is clinically relevant, as targeted therapies for SMARC-deficient tumors are currently being investigated and new clinical trial data show therapeutic benefit.